Fixed-base simulator investigation of lightweight vehicles for lunar escape to orbit with kinesthetic attitude control and simplified manual guidance

Piloted simulator investigation of lightweight vehicles for emergency lunar escape to orbit with kinesthetic attitude control and simplified manual guidanc

Development of a simulator for studying simplified lunar escape systems

Design and development of lunar escape system simulator for investigation of lunar escape problems and simplified manual guidance and control for lunar escape vehicle

Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock

During heat shock and other proteotoxic stresses, cells regulate multiple steps in gene expression in order to globally repress protein synthesis and selectively upregulate stress response proteins. Splicing of several mRNAs is known to be inhibited during heat stress, often meditated by SRp38, but the extent and specificity of this effect have remained unclear. Here, we examined splicing regulation genome-wide during heat shock in mouse fibroblasts. We observed widespread retention of introns in transcripts from ~1,700 genes, which were enriched for tRNA synthetase, nuclear pore, and spliceosome functions. Transcripts with retained introns were largely nuclear and untranslated. However, a group of 580+ genes biased for oxidation reduction and protein folding functions continued to be efficiently spliced. Interestingly, these unaffected transcripts are mostly cotranscriptionally spliced under both normal and stress conditions, whereas splicing-inhibited transcripts are mostly spliced posttranscriptionally. Altogether, our data demonstrate widespread repression of splicing in the mammalian heat stress response, disproportionately affecting posttranscriptionally spliced genes.Weizmann Institute of Science (Postdoctoral Award for Advancing Women in Science)European Molecular Biology Organization (Long-term Fellowship)Machiah FoundationNational Science Foundation (U.S.) (Grant 0821391)National Institutes of Health (U.S.

Wilson ratio in Yb-substituted CeCoIn5

We have investigated the effect of Yb substitution on the Pauli limited, heavy fermion superconductor, CeCoIn$_5$. Yb acts as a non-magnetic divalent substituent for Ce throughout the entire doping range, equivalent to hole doping on the rare earth site. We found that the upper critical field in (Ce,Yb)CoIn$_5$ is Pauli limited, yet the reduced (H,T) phase diagram is insensitive to disorder, as expected in the purely orbitally limited case. We use the Pauli limiting field, the superconducting condensation energy and the electronic specific heat coefficient to determine the Wilson ratio ($R_{W}$), the ratio of the specific heat coefficient to the Pauli susceptibility in CeCoIn$_5$. The method is applicable to any Pauli limited superconductor in the clean limit.Comment: 5 pages, 1 table, 4 figure

Implementing effective community-based surveillance in research studies of maternal, newborn and infant outcomes in low resource settings

BACKGROUND: Globally adopted health and development milestones have not only encouraged improvements in the health and wellbeing of women and infants worldwide, but also a better understanding of the epidemiology of key outcomes and the development of effective interventions in these vulnerable groups. Monitoring of maternal and child health outcomes for milestone tracking requires the collection of good quality data over the long term, which can be particularly challenging in poorly-resourced settings. Despite the wealth of general advice on conducting field trials, there is a lack of specific guidance on designing and implementing studies on mothers and infants. Additional considerations are required when establishing surveillance systems to capture real-time information at scale on pregnancies, pregnancy outcomes, and maternal and infant health outcomes. MAIN BODY: Based on two decades of collaborative research experience between the Kintampo Health Research Centre in Ghana and the London School of Hygiene and Tropical Medicine, we propose a checklist of key items to consider when designing and implementing systems for pregnancy surveillance and the identification and classification of maternal and infant outcomes in research studies. These are summarised under four key headings: understanding your population; planning data collection cycles; enhancing routine surveillance with additional data collection methods; and designing data collection and management systems that are adaptable in real-time. CONCLUSION: High-quality population-based research studies in low resource communities are essential to ensure continued improvement in health metrics and a reduction in inequalities in maternal and infant outcomes. We hope that the lessons learnt described in this paper will help researchers when planning and implementing their studies

Motion-base simulator study of control of an externally blown flap STOL transport aircraft after failure of an outboard engine during landing approach

A moving-base simulator investigation of the problems of recovery and landing of a STOL aircraft after failure of an outboard engine during final approach was made. The approaches were made at 75 knots along a 6 deg glide slope. The engine was failed at low altitude and the option to go around was not allowed. The aircraft was simulated with each of three control systems, and it had four high-bypass-ratio fan-jet engines exhausting against large triple-slotted wing flaps to produce additional lift. A virtual-image out-the-window television display of a simulated STOL airport was operating during part of the investigation. Also, a simple heads-up flight director display superimposed on the airport landing scene was used by the pilots to make some of the recoveries following an engine failure. The results of the study indicated that the variation in visual cues and/or motion cues had little effect on the outcome of a recovery, but they did have some effect on the pilot's response and control patterns

Widespread Regulation of Translation by Elongation Pausing in Heat Shock

Global repression of protein synthesis is a hallmark of the cellular stress response and has been attributed primarily to inhibition of translation initiation, although this mechanism may not always explain the full extent of repression. Here, using ribosome footprinting, we show that 2 hr of severe heat stress triggers global pausing of translation elongation at around codon 65 on most mRNAs in both mouse and human cells. The genome-wide nature of the phenomenon, its location, and features of protein N termini suggested the involvement of ribosome-associated chaperones. After severe heat shock, Hsp70’s interactions with the translational machinery were markedly altered and its association with ribosomes was reduced. Pretreatment with mild heat stress or overexpression of Hsp70 protected cells from heat shock-induced elongation pausing, while inhibition of Hsp70 activity triggered elongation pausing without heat stress. Our findings suggest that regulation of translation elongation in general, and by chaperones in particular, represents a major component of cellular stress responses.National Institute of General Medical Sciences (U.S.) (NIGMS fellowship number F32GM095060)Machiah FoundationEuropean Molecular Biology Organization (EMBO long-term fellowship)Weitzmann Institute of Science (National Postdoctoral Award Program for Advancing Women in Science

Repeat Human Immunodeficiency Virus Testing by Transmission Risk Group and Rurality of Residence in North Carolina

Background Understanding of repeat human immunodeficiency virus (HIV) testing (RHT) is limited and the impact of rural residence as a potential barrier to RHT is unknown. Rural populations are of particular interest in the Southeastern United States because of their disproportionate HIV burden. Methods We used HIV surveillance data from publicly funded HIV testing sites in North Carolina to assess repeat testing by transmission risk group and residential rurality in a retrospective cohort study. Linear binomial regression models were used to estimate adjusted, 1-year cumulative incidences and cumulative incidence differences comparing RHT within transmission risk populations by level of rurality. Results In our total study population of 600,613 persons, 19,275 (3.2%) and 9567 (1.6%) self-identified as men who have sex with men (MSM) and persons who inject drugs (PWID), respectively. A small minority, 13,723 (2.3%) resided in rural ZIP codes. Men who have sex with men were most likely to repeat test (unadjusted, 1-year cumulative incidence after an initial negative test, 16.4%) compared with PWID (13.2%) and persons who did not identify as either MSM or PWID (13.6%). The greatest effect of rurality was within PWID; the adjusted, 1-year cumulative incidence of RHT was 6.4 (95% confidence interval, 1.4-11.4) percentage points higher among metropolitan versus rural PWID. Conclusions One-year cumulative incidence of RHT was low among all clients of publicly funded HIV testing sites in North Carolina, including MSM and PWID for whom annual testing is recommended. Our findings suggest a need for public health efforts to increase access to and support for RHT, particularly among rural PWID

A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials

<p>Abstract</p> <p>Background</p> <p>The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures.</p> <p>Results</p> <p>Carbon black particles (Printex 90) and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs). Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm²) of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D <it>in vitro </it>model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1) as well as profibrotic (M2) phenotypic markers.</p> <p>Conclusions</p> <p>Induction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model offers a time- and cost-effective platform to evaluate the potential of engineered high aspect ratio nanomaterials, including carbon nanotubes, nanofibers, nanorods and metallic nanowires, to induce granulomas following inhalation.</p